Identification of a novel class of genomic DNA-binding sites suggests a mechanism for selectivity in target gene activation by the tumor suppressor protein p53

Identification of a novel class of genomic DNA-binding sites suggests a mechanism for selectivity in target gene activation by the tumor suppressor protein p53
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DOI:
10.1101/gad.12.14.2102
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发表时间:
1998-07-15
影响因子:
10.5
通讯作者:
Manfredi, JJ
Manfredi, JJ
中科院分区:
生物学1区
文献类型:
--
作者:
Resnick-Silverman, L;St Clair, S;Manfredi, JJ

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在细胞周期蛋白依赖性激酶抑制剂p21的基因启动子中有两个p53的反应元件。用单克隆抗体421孵育可增强p53与5'位点的结合,而抑制p53与3'位点的结合。突变分析表明,单个碱基的改变会导致一个元件的行为与另一个元件相似。人cdc25C启动子中的1h应答元件被p53结合,具有与3'位点相似的性质。这些结果确定了两类p53结合位点,并提出了靶基因选择性的p53的机制。
There are two response elements for p53 in the promoter of the gene for the cyclin-dependent kinase inhibitor p21. The binding of p53 to the 5' site was enhanced by incubation with monoclonal antibody 421, whereas the binding of p53 to the 3' site was inhibited. Mutational analysis showed that a single-base change caused one element to behave like the other. ih response element in the human cdc25C promoter is bound by p53 with properties similar to the 3' site. These results identify two classes of p53-binding sites and suggest a mechanism for target gene selectivity by p53.